Understanding process effects on the stability of amorphous form products (recrystallization of amorphous form products)

目的：该项目的目的是了解各种工艺如何影响药物递送无定形形式产品的稳定性，以限制其重结晶。这些目标可以大致分为三个方面：通过两种不同的路线制备的模型药物释放系统的表征，并在一系列条件下储存确定影响模型系统稳定性的关键分子因素（例如实验设计）开发更通用的预测模型和分子指纹图谱方法学：药物释放系统的表征是该项目的关键方面。电子显微镜和X射线衍射等技术将用于识别非晶态内的纳米级结晶区域，这些区域可能会引发材料的重组，从而导致产品不稳定。这将允许确定尺寸、形态和结构，从而允许对样品内的结晶区域进行时空评估。该过程不仅是时间依赖性的，而且还受用于产生无定形形式的制剂类型和过程的影响。一旦开发出可靠的方法，就可以开发出与从不同生产方法开发的样品的相关性。该项目还将研究从表征中开发的模拟和模型，因为它们可用于在测试前预测配方特性。预测模型与已建立的数据，将是至关重要的预测活性成分和药物输送系统的结晶。潜在影响：该项目的影响将出现在需要无定形产品的领域，例如医学中的许多药物。在这种情况下，如果产品不稳定并结晶，可能会影响功效。在开发识别、理解并最终预测这种结晶的方法时，我们将能够考虑加工和储存条件的影响。

Aims:The aim of the project is to understand how various processes influence the stability of drug delivery amorphous form products, in order to limit their recrystallisation. These objectives could roughly be divided into three aspects: Characterisation of model drug delivery systems, prepared via two different routes, and stored in a range of conditionsIdentification of the key molecular factors that affect the stability of the model systems (e.g. designing of experiments)Development of more general predictive models and molecular fingerprints.Methodology:Characterisation of the drug delivery systems is the key aspect of the project. Techniques such as electron microscopy and X-ray diffraction will be used to identify nano-sized crystalline regions within the amorphous state that may initiate re-structuring of the material, and thus lead to product instability. This will allow determination of the size, morphology and structure allowing a tempero-spatial assessment of crystalline areas within the sample. Not only is this process time-dependent but is affected by the type of formulation and processes used to generate the amorphous form. Once reliable methods are developed, a correlation with samples that are developed from different production methods can be developed. The project will also look at simulations and models developed from the characterisation, as they can be utilised to predict formulation properties prior to testing. Predictive models with the established data, would be crucial for predicting the crystallisation of active ingredients and drug delivery systems. Potential Impact: The impact of this project will be in areas where an amorphous product is desired, such as with many drugs within medicine. In this instance, if the products are unstable, and crystallise, this may affect the efficacy. In developing methods to identify, then understand and ultimately predict this crystallisation, we will be able to consider the effects of processing and storage conditions.